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Aluminium hydroxide potentiates a protective Th1 biased immune response against polio virus that allows for dose sparing in mice and rats
Institution:1. Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark;2. Department of Vaccine Development, Statens Serum Institut, Copenhagen, Denmark;1. HealthCore, Inc., 800 Delaware Avenue, Fifth Floor, Wilmington, DE 19801, United States;2. Department of Epidemiology, Merck Research Laboratories, 351 N. Sumneytown Pike, North Wales, PA 19454, United States;1. Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 211198, China;2. Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu Province, 211198, China;3. Department of Pharmacy, Jiangsu Jiankang Vocational College, Nanjing, Jiangsu Province, 211198, China;4. Department of Surgery, Nanjing Shuiximen Hospital, Nanjing, Jiangsu Province, 211198, China;5. Zhongda Hospital, Affiliated with Southeast University, Nanjing, Jiangsu Province, 210017, China
Abstract:BackgroundThe development of new low cost inactivated polio virus based vaccines (IPV) is a high priority and will be essential for the complete eradication of polio. Since the aluminium hydroxide adjuvant is widely used in humans we tested this adjuvant with IPV in two models. Our objective was twofold; to examine the IPV dose sparing effect of aluminium hydroxide and how the adjuvant effect of aluminium hydroxide affected the immunity induced by IPV.MethodsMice and rats were immunized with IPV formulated with Aluminium hydroxide and subjected to immunological analyses and serum polio virus neutralization titer determination.ResultsAddition of aluminium hydroxide to IPV led to a ten times dose sparing effect compared to IPV alone, measured by virus neutralization titers in serum. Aluminium hydroxide changed the kinetics of the response against IPV leading to a faster and stronger response, which due to IPV induced immune dominance was characterized as a strong Th1-biased cellular/humoral immune response.ConclusionsThe IPV-aluminium hydroxide formulation constitutes a promising vaccine capable of generating strong Th1 immunity against infection with all three serotypes. A phase I/II clinical study was recently initiated.
Keywords:Vaccination  Th1/Th2 cells  Viral infection  Adjuvant  Polio  Dose sparing
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